Impact of methimazole-induced hypothyroidism on postnatal swine.

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.

Apathetic Graves' disease with severe hepatic and renal dysfunction induced by COVID-19 infection: Case report and literature review.

RATIONALE: A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic. PATIENT CONCERN: A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month. DIAGNOSIS: Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy. INTERVENTION: Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy. OUTCOME: After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later. CONCLUSION: COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.

An unusual evolution of thyroid function after therapeutic plasma exchange in Graves' disease with cholestatic jaundice: A case report.

RATIONALE: Methimazole (MMI) is the first-line agent in the treatment of hyperthyroidism. However, rare but severe cholestatic jaundice may occur. Therapeutic plasma exchange (TPE) may provide an alternative treatment for such patients and they received thyroidectomy/radioactive iodine ablation or continued oral anti hyperthyroidism medication immediately after TPE session in the reported literatures. The case reported here is, to our knowledge, the first to describe the long interval between anti hyperthyroidism therapy and TPE in such patients. PATIENT CONCERNS: A 49-year-old Chinese woman had developed worsening jaundice 3 weeks after receiving methimazole (20 mg/day) for the treatment of hyperthyroidism secondary to Graves' disease (GD). Additionally, she had a 2-year history of type 2 diabetes. DIAGNOSIS: Hyperthyroidism secondary to GD, MMI-induced severe cholestatic jaundice and type 2 diabetes. INTERVENTIONS: Methimazole was discontinued and the patient received 3 times of TPE, about 3-month glucocorticoid treatment, insulin administration accordingly and other conventional liver-protecting therapy. OUTCOMES: Her thyroid function was stabilized with small dose of thyroxine substitution and euthyroid status persisted after thyroxine discontinuation until hyperthyroidism recurred 7 months later while her cholestatic jaundice was eventually recovered by about 3-month glucocorticoid therapy. LESSONS: Due to the complex interplay between liver function and thyroid hormones, there may be unusual changes of thyroid function in GD patients with severe liver injury after TPE. By this case, we want to highlight the importance of a closely following up of thyroid function in order to deliver appropriate health suggestions for patients.

Radioactive Iodine Therapy of Graves' Disease in Patients Pretreated With Methimazole Without Radioiodine Uptake for Dose Estimation.

OBJECTIVE: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole. METHODS: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies. RESULTS: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response. CONCLUSION: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.

Thyroid hormone resistance and large goiter mimicking infiltrative carcinoma in a pediatric patient.

OBJECTIVES: Resistance to thyroid hormone (RTH) is a genetic condition, caused by mutations in the thyroid hormone receptor gene and characterized by impaired end organ responsiveness to thyroid hormone. Here we describe a novel case of THR associated with large goiter mimicking infiltrative c. CASE PRESENTATION: A 13-year-old male with a hyperthyroid phenotype of RTH diagnosed as a toddler, on methimazole and nadolol therapies presented with an increase in goiter size and possible nodule. Thyroid ultrasound was concerning for a diffuse infiltrative process or malignancy. Methimazole was discontinued and he underwent further imaging, fine needle aspiration and core biopsies. Biopsy results were reassuring and imaging findings were subsequently attributed to RTH rather than malignancy. He started every other day liothyronine therapy, which led to a decrease in goiter size, thyroglobulin level, and improvement of hyperthyroid symptoms. CONCLUSIONS: This is the first case to our knowledge describing the above thyroid imaging findings in association with RTH. It also adds important information to the pediatric literature regarding management of the hyperthyroid phenotype of RTH, including the role of liothyronine therapy.

Fe single atoms encapsulated in N, P-codoped carbon nanosheets with enhanced peroxidase-like activity for colorimetric detection of methimazole.

Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV-vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5-50 mM and a LOD of 1.57 mM, coupled by assay of H2O2 at a linear range of 3-50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.

Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019).

CONTEXT: In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking. OBJECTIVE: The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program. METHODS: From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism. RESULTS: The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 µg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%. CONCLUSION: Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.

The influence of thionamides on intra-thyroidal uptake of 131I during radioiodine-131 treatment of Graves' disease.

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

Case report: Severe cholestatic jaundice associated with hyperthyroidism treated with methimazole.

RATIONALE: We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment. PATIENT CONCERNS: The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases. DIAGNOSIS: The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out. OUTCOMES: The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function. LESSONS: The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

A review on nondiabetic hypoglycemia from various causes: Case series report.

RATIONALE: Hypoglycemia is common in patients with glucose regulation disorders and related diabetic treatments but is rare in nondiabetic patients. Severe hypoglycemia can cause harm to patients' cognition, consciousness, central nervous system, cardiovascular and cerebrovascular system, and even death. However, the most fundamental way to control hypoglycemia is to identify the cause and deal with the primary disease. This article introduces 3 cases of nondiabetic hypoglycemia with different causes, aiming to improve our understanding of nondiabetic hypoglycemia and improve the ability of early diagnosis and differential diagnosis. PATIENT CONCERNS: Case 1 is a 19-year-old female with a history of recurrent coma, and magnetic resonance imaging and endoscopic ultrasound of the pancreas suggest insulinoma. Case 2 is a 74-year-old male with a history of viral hepatitis, and computerized tomography shows multiple nodules in the liver, which is diagnosed as liver cancer. Case 3 is a 39-year-old female with a history of taking methimazole, who tested positive for insulin antibodies, and was diagnosed with insulin autoimmune syndrome. DIAGNOSIS: All 3 patients were diagnosed with nondiabetic hypoglycemia, but the causes varied, and included insulinoma, non-islet cell tumor-induced hypoglycemia, and insulin autoimmune syndrome. INTERVENTIONS: Case 1 underwent pancreatic tail resection; case 2 refused anti-tumor treatment and received glucose injections for palliative treatment only; and case 3 stopped taking methimazole. OUTCOMES: After surgery, the blood sugar in case 1 returned to normal, and the blood sugar in case 2 was maintained at about 6.0 mmol/L. The symptoms of hypoglycemia gradually improved in case 3 after stopping the medication. LESSONS: Non-diabetic hypoglycemia requires further examination to clarify the cause, and the correct differential diagnosis can provide timely and effective treatment, improving the patient's prognosis.

Oxidation of anti-thyroid drugs and their selenium analogs by ABTS radical cation.

Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Peroxidases oxidize ABTS to a metastable radical ABTS•+, which is readily reduced by many antioxidants, including thiol-containing compounds, and it has been used for decades to measure antioxidant activity in biological samples. We showed that anti-thyroid drugs 6-n-propyl-2-thiouracil, methimazole, and selenium analogs of methimazole also reduced it rapidly. This reaction may explain the anti-thyroid action of many other compounds, particularly natural antioxidants, which may reduce the oxidized form of iodine and/or tyrosyl radicals generated by thyroid peroxidase thus decreasing the production of thyroid hormones. However, influence of selenium analogs of methimazole on the rate of hydrogen peroxide consumption during oxidation of ABTS by lactoperoxidase was moderate. Direct hydrogen peroxide reduction, proposed before as their mechanism of action, cannot therefore account for the observed inhibitory effects. 1-Methylimidazole-2-selone and its diselenide were oxidized by ABTS•+ to relatively stable seleninic acid, which decomposed slowly to selenite and 1-methylimidazole. In contrast, oxidation of 1,3-dimethylimidazole-2-selone gave selenite and 1,3-dimethylimidazolium cation. Accumulation of the corresponding seleninic acid was not observed.

Different doses of methimazole treatment of children and adolescents with graves' disease: a clinical study based on 161 cases of outpatients.

OBJECTIVE: This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD. METHODS: One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed. RESULTS: After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%). CONCLUSIONS: Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.

Limits to sustained energy intake. XXXIII. Thyroid hormones play important roles in milk production but do not define the heat dissipation limit in Swiss mice.

The limits to sustained energy intake set physiological upper boundaries that affect many aspects of human and animal performance. The mechanisms underlying these limits, however, remain unclear. We exposed Swiss mice to either supplementary thyroid hormones (THs) or the inhibitor methimazole during lactation at 21 or 32.5°C, and measured food intake, resting metabolic rate (RMR), milk energy output (MEO), serum THs and mammary gland gene expression of females, and litter size and mass of their offspring. Lactating females developed hyperthyroidism following exposure to supplementary THs at 21°C, but they did not significantly change body temperature, asymptotic food intake, RMR or MEO, and litter and mass were unaffected. Hypothyroidism, induced by either methimazole or 32.5°C exposure, significantly decreased asymptotic food intake, RMR and MEO, resulting in significantly decreased litter size and litter mass. Furthermore, gene expression of key genes in the mammary gland was significantly decreased by either methimazole or heat exposure, including gene expression of THs and prolactin receptors, and Stat5a and Stat5b. This suggests that endogenous THs are necessary to maintain sustained energy intake and MEO. Suppression of the thyroid axis seems to be an essential aspect of the mechanism by which mice at 32.5°C reduce their lactation performance to avoid overheating. However, THs do not define the upper limit to sustained energy intake and MEO at peak lactation at 21°C. Another, as yet unknown, factor prevents supplementary thyroxine exerting any stimulatory metabolic impacts on lactating mice at 21°C.

Long-term follow-up after discharge witnesses a slow decline of insulin autoantibodies in patients with insulin autoimmune syndrome complicated with Grave's disease: a report of two cases.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization. CASE PRESENTATION: We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge. CONCLUSIONS: GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.

The Origin of Antithyroid Drugs.

Background: When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has been learned about their mechanism of action and clinical utility, they continue to be used today in much the same way as they have been since their introduction. Summary: In 1995, Dr. Clark Sawin gave an address on the history of antithyroid drug development at the 11th International Thyroid Congress in Toronto, Ontario, Canada. In his review, Dr. Sawin recounted the original observations by Drs. Julia and Cosmo Mackenzie and Curt Richter at the Johns Hopkins University School of Medicine, and how their work ultimately led to Dr. Edwin (Ted) B. Astwood's seminal 1943 report on the use of thiourea and thiouracil in the Journal of the American Medical Association. He also described the development of propylthiouracil and methimazole as less toxic alternatives. He concluded his remarks by noting the often-serendipitous pathway of drug development and the role of pharmaceutical companies in the process. Conclusions: Antithyroid drugs remain a cornerstone of thyroid therapeutics. It is informative to review the process by which they came into use, as this is a seminal part of the history of thyroid disease in the 20th century. This knowledge may also spark additional research leading to new pharmacotherapies for patients with hyperthyroidism.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 days after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e. proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

[Leukocytoclastic vasculitis as an adverse effect of propylthiouracil. A case report]. / Vasculitis leucocitoclástica como efecto adverso del propiltiouracilo. Reporte de un caso.

BACKGROUND: The most common cause of hyperthyroidism is Graves' disease. Propylthiouracil (PTU) is one of the drugs used to treat this disease. Leukocytoclastic vasculitis is described among dermatologic adverse effects of PTU. CASE REPORT: A 18-year-old woman, allergic to methimazole, developed a vasculitis associated to ANCAs with characteristics of leukocytoclastic vasculitis, associated to PTU treatment. She did not present systemic involvement. PTU treatment was suspended. Two months later, the skin lesions had almost completely resolved. CONCLUSIONS: Leukocytoclastic vasculitis should be considered in the spectrum of complications caused by the consumption of propylthiouracil. The lesions can manifest over time, from a few weeks to years after taking the drug. When there is no systemic involvement, propylthiouracil suspension is sufficient to cure the disease.

ANTECEDENTES: La causa más frecuente de hipertiroidismo es la enfermedad de Graves. El propiltiouracilo es uno de los medicamentos más prescritos para esta enfermedad. Uno de los efectos adversos dermatológicos del propiltiouracilo es la vasculitis leucocitoclástica. REPORTE DE CASO: Paciente femenina de 18 años, alérgica al metamizol, con vasculitis asociada a ANCAs, con características de vasculitis leucocitoclástica provocada por el consumo de propiltiouracilo. No se observó afectación sistémica. Dos meses después de suspender el propiltiouracilo desaparecieron casi por completo las lesiones en la piel. CONCLUSIONES: La vasculitis leucocitoclástica debe considerarse en el espectro de complicaciones provocadas por el consumo de propiltiouracilo. Las lesiones pueden manifestarse con el paso del tiempo, desde unas semanas hasta años después de consumir el fármaco. Cuando no existe afectación sistémica, la suspensión del propiltiouracilo es suficiente para detener la enfermedad.

Clinical manifestations and early effectiveness of methimazole in patients with graves' hyperthyroidism-related severe hepatic dysfunction.

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.

Long-term follow-up of methimazole-associated insulin autoimmune syndrome: a rare case report.

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of long-term follow-up of IAS in China is limited. We herein report a case of drug-induced IAS in a 44-year-old Chinese woman. She had been taking methimazole for Graves' disease and had subsequently presented with recurrent hypoglycemic episodes. Laboratory assessments on admission revealed that her serum insulin level was significantly elevated (>1000 µIU/mL) and that she was positive for serum insulin autoantibody, leading to a diagnosis of IAS. Human leukocyte antigen DNA typing identified *04:06/*09:01:02, an immunogenetic determinant associated with IAS. After treatment with prednisone for 2 months, the hypoglycemic episodes disappeared, her serum insulin level gradually declined, and her insulin antibody levels became negative. Clinicians should be aware of the potential for methimazole to trigger autoimmune hypoglycemia in people with a genetic predisposition.